The primary objective of the proposed research is to establish the physiological function and significance of polyamine acetylation in mammalian brain. Three physiological functions are proposed for polyamine acetylation and form the basis for the studies outlined in this proposal. It is proposed that acetylation of polyamines in the central nervous system: (1) may be involved in regulation of polyamine activity in the nervous system through effects on binding of polyamines to membranes, nucleic acids, or other "receptor" molecules; (2) may serve as an intermediate step in the further metabolism of polyamines to active neurotransmitter or modulator substances; and (3) may be involved in the processes of intracellular transport of polyamines or elimination of polyamines from the central nervous system. To achieve the overall objective of this project and to evaluate the proposals concerning the physiological function of polyamine acetylation, specific studies will be conducted aimed at determining: (1) the levels of acetylated polyamines occurring in the brain, (2) the routes of metabolism for acetylated polyamines in neural tissues, and (3) the pharmacologic actions of the acetylated polyamine derivatives in comparison to those of the parent compounds. It is expected that these studies will not only contribute to our basic knowledge of the metabolism and fate of polyamines in the brain but will also furnish new insight into the physiologic functions of these ubiquitous amines in the central nervous system.